Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity

Brown, Scott A., Stambas, John, Zhan, Xiaoyan, Slobod, Karen S., Coleclough, Chris, Zirkel, Amy, Surman, Sherri, White, Stephen W., Doherty, Peter C. and Hurwitz, Julia L. 2003, Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity, The Journal of Immunology, vol. 171, no. 8, pp. 4140-4148.

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Title Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity
Author(s) Brown, Scott A.
Stambas, JohnORCID iD for Stambas, John
Zhan, Xiaoyan
Slobod, Karen S.
Coleclough, Chris
Zirkel, Amy
Surman, Sherri
White, Stephen W.
Doherty, Peter C.
Hurwitz, Julia L.
Journal name The Journal of Immunology
Volume number 171
Issue number 8
Start page 4140
End page 4148
Publisher American Association of Immunologists
Place of publication Baltimore, Md.
Publication date 2003-10-15
ISSN 0022-1767
Summary A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6MT/MT mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4 T cell response profiles were characterized toward overlapping peptides using an IFN- ELISPOT assay. We found a striking similarity between the peptide response profiles in the two mouse strains. Profiles also matched those of previous experiments in which different envelope vaccination regimens were used. Our results clearly demonstrate that normal Ab activity is not required for the establishment or maintenance of Th peptide immunodominance in the HIV envelope response. To explain the clustering of Th cell epitopes, we propose that localization of peptide on exposed envelope surfaces facilitates proteolytic activity and preferential peptide shuttling through the Ag processing pathway.
Language eng
Field of Research 110804 Medical Virology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ┬ęCopyright 2003 by The American Association of Immunologists, Inc.
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